MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in BRAF-, NRAS -, and NF1 -Mutant Melanomas

• Published in: Cancer discovery Vol. 9; no. 4; pp. 526 - 545
• Main Authors: Maertens, Ophélia, Kuzmickas, Ryan, Manchester, Haley E, Emerson, Chloe E, Gavin, Alessandra G, Guild, Caroline J, Wong, Terence C, De Raedt, Thomas, Bowman-Colin, Christian, Hatchi, Elodie, Garraway, Levi A, Flaherty, Keith T, Pathania, Shailja, Elledge, Stephen J, Cichowski, Karen
• Format: Journal Article
• Language: English
• Published: United States 01.04.2019
• Subjects: DNA Repair - genetics; Genes, ras - genetics; Humans; MAP Kinase Kinase Kinases - genetics; Melanoma - genetics; Proto-Oncogene Proteins B-raf

Although the majority of -mutant melanomas respond to BRAF/MEK inhibitors, these agents are not typically curative. Moreover, they are largely ineffective in - and -mutant tumors. Here we report that genetic and chemical suppression of HDAC3 potently cooperates with MAPK pathway inhibitors in all th...